Concurrent versus individual binding of HuR and AUF1 to common labile target mRNAs
Open accessAbstract
RNA-binding proteins HuR and AUF1 bind to many common AU-rich target mRNAs and exert opposing influence on target mRNA stability, but the functional interactions between HuR and AUF1 have not been systematically studied. Here, using common target RNAs encoding p21 and cyclin D1, we provide evidence that HuR and AUF1 can bind target transcripts on both distinct, nonoverlapping sites, and on common sites in a competitive fashion. In the nucleus, both proteins were found together within stable ribonucleoprotein complexes; in the cytoplasm, HuR and AUF1 were found to bind to target mRNAs individually, HuR colocalizing with the translational apparatus and AUF1 with the exosome. Our results indicate that the composition and fate (stability, translation) of HuR- and/or AUF1-containing ribonucleoprotein complexes depend on the target mRNA of interest, RNA-binding protein abundance, stress condition, and subcellular compartment.
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These interactions require the presence of RNA, since HuR and AUF1 were shown to simultaneously or competitively bind onto exclusive or common cis-acting elements in the 3′ UTRs of p21cip1/waf1, Cyclin D, TNFα, and β2-adrenergic receptor mRNAs.
“Moreover, these interactions require the presence of RNA, since HuR and AUF1 were shown to simultaneously or competitively bind onto exclusive or common, respectively, cis-acting elements in the 3′ UTRs of p21cip1/waf1, Cyclin D, TNFα, and β2-adrenergic receptor mRNAs (Lal et al. 2004; David et al. 2007).”
From Emerging complexity of the HuD/ELAVl4 gene; implications for neuronal development, function, and dysfunction (2013) · cites this paper as Lal et al. 2004
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- Authors
- Lal, A., Mazan‐Mamczarz, K., Kawai, T., Yang, X., Martindale, J. L., & Gorospe, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Gorospe, Myriam
- Venue
- The EMBO Journal
- Published
- 2004-07-15
- Volume
- 23
- Issue
- 15
- Pages
- 3092-3102
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC514922
- OpenAlex
- W2159376549
- Cited by
- 461
- References
- 1
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 8 · 2023: 11 · 2022: 7 · 2021: 9 · 2020: 19 · 2019: 11 · 2018: 14 · 2017: 15 · 2016: 19 · 2015: 20 · 2014: 37 · 2013: 28 · 2012: 36
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Keywords
- HuR, AUF1, AU-rich elements, mRNA stability, RNA-binding proteins, competitive binding, ribonucleoprotein complexes, p21, cyclin D1, exosomes, translational regulation, stress response
- MeSH terms
- ELAV-Like Protein 1, Heterogeneous Nuclear Ribonucleoprotein D0, Antigens, Surface, Gene Expression Regulation, HeLa Cells, Humans, RNA, Messenger, Substrate Specificity, Transcription, Genetic, Ultraviolet Rays, RNA-Binding Proteins, Cell Cycle Proteins, Cyclin D1, RNA Stability, Heterogeneous-Nuclear Ribonucleoprotein D, RNA, Small Interfering, Cyclin-Dependent Kinase Inhibitor p21, ELAV Proteins
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